As cancer research progresses, it is increasingly evident that single drug formulations provide only limited treatment success. Patients would therefore benefit from the development of suitable combination therapies. One of the most important requirements of combination therapy is a simple and efficacious drug delivery system. Many currently used chemotherapeutics are poorly water soluble, which significantly complicates the process of partnering the chemotherapeutic with a suitable delivery system. Combining two or three drugs in a formulation presents additional challenges in clinical practice because of compatibility and stability issues. Safer and more effective delivery of drug combinations relies on the development of biocompatible delivery systems capable of solubilizing the drug combination without using harsh surfactants or excipients. Stable and biocompatible drug formulations that improve bioavailability without causing toxicity are urgently needed in the field of cancer research and therapy.
One of the fundamental features of cancer is deregulation of apoptosis. Apoptosis occurs following the triggering of cell surface death receptors (the extrinsic pathway) or after the perturbation of mitochondria (the intrinsic pathway). Members of the Bcl-2 family control the integrity of the outer mitochondrial membrane and are therefore important targets for inducing apoptosis via the intrinsic pathway. The resistance of many tumors to chemotherapy is associated with high levels of antiapoptotic Bcl-2 family members. Gossypol has been identified as an effective inhibitor of Bcl-2 proteins, although gossypol has very low aqueous solubility and effective drug delivery systems are needed for its further development as a clinical therapy.
Accordingly, stable and biocompatible drug formulations that improve bioavailability without causing toxicity are needed for improving cancer therapy. An effective drug delivery system for solubilizing Bcl-2 inhibitors, such as gossypol, is also needed. A drug delivery vehicle that can solubilize efficacious drug combinations, preferably without the use of pharmaceutical excipients that result in treatment complications, would significantly advance clinical cancer therapy. An effective combination drug therapy regimen that targets more than one cancer cell growth mechanistic pathway would also significantly aid cancer research and the development of effective clinical therapies.